Fluorinated analogs of nucleosides and fluorinated tracers of gene expression for positron emission tomography

F-18-FDG is currently the only fluorinated tracer used in routine clinical positron emission tomography (PET). Fluorine 18 is considered as the ideal radioisotope for PET, thanks to a low positron energy, which not only limits the dose rate to the patients but also provides high-resolution images. Furthermore, the 110 min. physical half-life allows for high-yield radiosynthesis, transport from the production site to the imaging site, and imaging protocols that could span hours, which permits dynamic studies and assessing metabolic processes that may be fairly slow Recently, synthesis of fluorinated tracers from prosthetic group precursors, which allows easier radiolabeling of biomolecules, has given a boost to the development of numerous fluorinated tracers, Given the wide availability of fluorine 18, such tracers may well develop into important routine tracers. This article is a review of the literature concerning fluorinated analogs of nucleosides and fluorinated radiotracers of gene expression recently developed and under investigation

Health status determinants: lifestyle, environment, health care resources and efficiency

This paper aims to shed light on the contribution of health care and other determinants to the health status of the population and to provide evidence on whether or not health care resources are producing similar value for money across OECD countries. First, it discusses the pros and cons of various indicators of the health status, concluding that mortality and longevity indicators have some drawbacks but remain the best available proxies. Second, it suggests that changes in health care spending, lifestyle factors (smoking and alcohol consumption as well as diet), education, pollution and income have been important factors behind improvements in health status. Third, it derives estimates of countries’ relative performance in transforming health care resources into longevity from two different methods – panel data regressions and data envelopment analysis – which give remarkably consistent results. The empirical estimates suggest that potential efficiency gains might be large enough to raise life expectancy at birth by almost three years on average for OECD countries, while a 10% increase in total health spending would increase life expectancy by three to four months

Is 3'-deoxy-3'- [18F] fluorothymidine ([18F]-FLT) the next tracer for routine clinical PET after R [18F]-FDG?

Positron emission tomography (PET) with [18F]-FDG is now firmly established as a clinical tool in oncology. Its applications are however limited in some indications, due to the lack of specificity of its uptake mechanism for tumors, or the low avidity of some cancer types such as prostate. Alternative tracers are thus being developed, in order to fill up this void. Proliferation as a biological target is particularly attractive in cancer imaging. From that perspective, fluorothymidine ([18F]-FLT or FLT) has generated a strong interest among the scientific community, especially since the radiosynthesis process has been improved and simplified, thus making possible to envision a routine use for the tracer. This article aims at summarizing the status of the current scientific data regarding FLT. The uptake mechanism of FLT is well known, relying on the thymidine kinase 1 (TK1) enzymatic activity, and thus on DNA synthesis. Preclinical studies have shown a clear relationship between tracer accumulation and level of tumor proliferation, even though DNA salvage pathwayss intervene in the process and may complicate the interpretation of the results. Several clinical studies suggest a good specificity for tumor, albeit with a lower sensitivity than with FDG. In all likelihood however, the future of FLT lies in the evaluation of antitumor response and possibly the pretherapeutic prognostic characterization, rather than in the diagnosis and staging of malignancies. Although the scientific data regarding this issue remain limited, initial results are encouraging. Further significant work remains to be done in order to fully assess the clinical performances of the tracer, on the one hand, and to determine its place relative to FDG and other emerging tracers, on the other hand. Until these studies are completed, FLT should be considered as a promising tracer, but remaining at an experimental stage of its development

Is 3 '-deoxy-3 '-[F-18] fluorothymidine ([F-18]-FLT) the next tracer for routine clinical PET after R [F-18]-FDG?

Positron emission tomography (PET) with {F-18}-FDG is nowfirmly established as a clinical tool in oncology. Its applications are however limited in some indications, due to the lack of specificity of its uptake mechanism for tumors, or the low avidity of some cancer types such as prostate. Alternative tracers are thus being developed, in order to fill up this void. Proliferation as a biological target is particularly attractive in cancer imaging. From that perspective, fluorothymidine ({F-18}-FLT or FLT) has generated a strong interest among the scientific community, especially since the radiosynthesis process has been improved and simplified, thus making possible to envision a routine use for the tracer. This article aims at summarizing the status of the current scientific data regarding FLT The uptake mechanism of FLT is well known, relying on the thymidine kinase 1 (TK1) enzymatic activity, and thus on DNA synthesis, Preclinical studies have shown a clear relationship between tracer accumulation and level of tumor proliferation, even though DNA salvage pathwayss intervene in the process and may complicate the interpretation of the results. Several clinical studies suggest a good specificity for tumor, albeit with a lower sensitivity than with FDG. In all likelihood however, the future of FLT lies in the evaluation of antitumor response and possibly the pretherapeutic prognostic characterization, rather than in the diagnosis and staging of malignancies. Although the scientific data regarding this issue remain limited, initial results are encouraging. Further significant work remains to he done in order to fully assess the clinical performances of the tracer, on the one hand, and to determine its place relative to FDG and other emerging tracers, on the other hand. Until these studies are completed, FLT should he considered as a promising tracer, hut remaining at an experimental stage of its development

Fluorinated tracers for imaging cancer with positron emission tomography

2-[F-18]fluoro-2-deoxy-D-glucose (FDG) is currently the only fluorinated tracer used in routine clinical positron emission tomography (PET). Fluorine-18 is considered the ideal radioisotope for PET imaging owing to the low positron energy (0.64 MeV), which not only limits the dose rate to the patient but also results in a relatively short range of emission in tissue, thereby providing high-resolution images. Further, the 110-min physical half-life allows for high-yield radiosynthesis, transport from the production site to the imaging site and imaging protocols that may span hours, which permits dynamic studies and assessment of potentially fairly slow metabolic processes. The synthesis of fluorinated tracers as an alternative to FDG was initially tested using nucleophilic fluorination of the molecule, as performed when radiolabelling with iodine-124 or bromide-76. However, in addition to being long, with multiple steps, this procedure is not recommended for bioactive molecules containing reactive groups such as amine or thiol groups. Radiochemical yields are also often low. More recently, radiosynthesis from prosthetic group precursors, which allows easier radiolabelling of biomolecules, has led to the development of numerous fluorinated tracers. Given the wide availability of 18F, such tracers may well develop into important routine tracers. This article is a review of the literature concerning fluorinated radiotracers recently developed and under investigation for possible PET imaging in cancer patients. Two groups can be distinguished. The first includes "generalist" tracers, i.e. tracers amenable to use in a wide variety of tumours and indications, very similar in this respect to FDG. These are tracers for non-specific cell metabolism, such as protein synthesis, amino acid transport, nucleic acid synthesis or membrane component synthesis. The second group consists of "specific" tracers for receptor expression (i.e. oestrogens or somatostatin), cell hypoxia or bone metabolism

Radioimmunothérapie Alpha du myélome multiple (étude préclinique in vitro avec le bismuth 213)

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Plaisance et urbanité. L’intégration des ports dans les villes contemporaines

International audienc